Furosemide stimulation of parathormone in humans: role of the calcium-sensing receptor and the renin-angiotensin system

Marie-Eve Muller, Valentina Forni Ogna, Marc Maillard, Candice Stoudmann, Carole Zweiacker, Christiane Anex, Grégoire Wuerzner, Michel Burnier, Olivier Bonny, Marie-Eve Muller, Valentina Forni Ogna, Marc Maillard, Candice Stoudmann, Carole Zweiacker, Christiane Anex, Grégoire Wuerzner, Michel Burnier, Olivier Bonny

Abstract

Interactions between sodium and calcium regulating systems are poorly characterized but clinically important. Parathyroid hormone (PTH) levels are increased shortly after furosemide treatment by an unknown mechanism, and this effect is blunted by the previous administration of a calcimimetic in animal studies. Here, we explored further the possible underlying mechanisms of this observation in a randomized crossover placebo-controlled study performed in 18 human males. Volunteers took either cinacalcet (60 mg) or placebo and received a 20 mg furosemide injection 3 h later. Plasma samples were collected at 15-min intervals and analyzed for intact PTH, calcium, sodium, potassium, magnesium, phosphate, plasma renin activity (PRA), and aldosterone up to 6 h after furosemide injection. Urinary electrolyte excretion was also monitored. Subjects under placebo presented a sharp increase in PTH levels after furosemide injection. In the presence of cinacalcet, PTH levels were suppressed and marginal increase of PTH was observed. No significant changes in electrolytes and urinary excretion were identified that could explain the furosemide-induced increase in PTH levels. PRA and aldosterone were stimulated by furosemide injection but were not affected by previous cinacalcet ingestion. Expression of NKCC1, but not NKCC2, was found in parathyroid tissue. In conclusion, our results indicate that furosemide acutely stimulates PTH secretion in the absence of any detectable electrolyte changes in healthy adults. A possible direct effect of furosemide on parathyroid gland needs further studies.

Keywords: Calcium-sensing receptor; Cinacalcet; Furosemide; Mineral metabolism; Renin-angiotensin-aldosterone system.

References

    1. Nephrol Dial Transplant. 1992;7(1):8-15
    1. Hypertension. 2014 Feb;63(2):273-80
    1. Nephrol Dial Transplant. 2011 Aug;26(8):2438-44
    1. Science. 2007 Jun 15;316(5831):1615-8
    1. Eur J Clin Invest. 2001 Sep;31(9):764-72
    1. Kidney Int. 2004 May;65(5):1684-9
    1. Endocrinology. 1991 Jul;129(1):489-95
    1. Br J Clin Pharmacol. 2007 Dec;64(6):804-9
    1. J Clin Invest. 1973 Jan;52(1):134-42
    1. Nephrol Dial Transplant. 2001 Dec;16(12 ):2303-9
    1. Pediatrics. 1982 Sep;70(3):360-3
    1. J Hypertens. 2009 Oct;27(10 ):1980-7
    1. Kidney Int. 2011 Apr;79(7):742-8
    1. Acta Endocrinol (Copenh). 1989 Mar;120(3):362-8
    1. J Endocrinol. 1987 Mar;112(3):431-7
    1. J Clin Endocrinol Metab. 2014 Mar;99(3):965-71
    1. Eur J Pediatr. 1999 Aug;158(8):668-72
    1. Surgery. 2009 Dec;146(6):1035-41
    1. Hypertension. 2011 Sep;58(3):341-6
    1. Am J Physiol Endocrinol Metab. 2001 Feb;280(2):E209-13
    1. Eur J Clin Pharmacol. 1980 Oct;18(4):363-4
    1. Hypertension. 2007 Oct;50(4):737-43
    1. Biol Neonate. 1998;73(5):306-12
    1. Endocrinology. 1983 Jul;113(1):371-8
    1. Nephron. 1984;38(2):109-14
    1. Ann Intern Med. 1972 Oct;77(4):587-91
    1. J Hypertens. 2012 Feb;30(2):390-5
    1. Am J Physiol Renal Physiol. 2005 Dec;289(6):F1185-92
    1. J Clin Endocrinol Metab. 1997 Jan;82(1):281-6
    1. Metabolism. 1987 Jan;36(1):36-42
    1. J Clin Endocrinol Metab. 1992 Oct;75(4):988-92

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